BILHI Genetics, 60 Avenue André Roussin, 13016, Marseille, France.
UMR_S906-Génétique Et Immunologie Des Maladies Parasitaires, Aix Marseille Université-INSERM, Marseille, France.
Hum Genet. 2020 Jun;139(6-7):821-831. doi: 10.1007/s00439-020-02160-4. Epub 2020 Apr 10.
Schistosomes induce severe hepatic disease, which is fatal in 2-10% of cases, mortality being higher in cases of co-infection with HBV or HCV. Hepatic disease occurs as a consequence of the chronic inflammation caused by schistosome eggs trapped in liver sinusoids. In certain individuals, the repair process leads to a massive accumulation of fibrosis in the periportal spaces. We and others have shown that genetic variants play a crucial role in disease progression from mild to severe fibrosis and explain why hepatic fibrosis progresses rapidly in certain subjects only. We will review here published findings concerning the strategies that have been used in the analysis of hepatic fibrosis in schistosome-infected individuals, the genetic variants that have associated with fibrosis, and variants in new pathways crucial for fibrosis progression. Together, these studies show that the development of fibrosis is under the tight genetic control of various common variants with moderate effects. This polygenic control has made it possible to develop models that identify schistosome-infected individual at risk of severe hepatic disease. We discuss the performances and limitations of these models.
血吸虫会导致严重的肝脏疾病，在 2-10%的病例中是致命的，在合并感染乙型肝炎病毒或丙型肝炎病毒的情况下死亡率更高。肝脏疾病是由滞留在肝窦的血吸虫卵引起的慢性炎症引起的。在某些个体中，修复过程会导致门脉周围空间大量纤维组织的积累。我们和其他人已经表明，遗传变异在从轻度到重度纤维化的疾病进展中起着至关重要的作用，并解释了为什么肝纤维化在某些个体中会迅速进展。我们将在这里回顾已经发表的关于分析血吸虫感染者肝纤维化的策略的研究结果、与纤维化相关的遗传变异，以及在纤维化进展中至关重要的新途径的变异。这些研究表明，纤维化的发展受到各种常见变异的严格遗传控制，这些变异的影响程度中等。这种多基因控制使得开发模型成为可能，这些模型可以识别出患有严重肝脏疾病风险的血吸虫感染者。我们讨论了这些模型的性能和局限性。
